Anacetrapib
A high-fat meal can raise anacetrapib exposure up to eight-fold, but age, sex, and obesity barely move it (Br J Clin Pharmacol 2009)
Original title: Single-dose pharmacokinetics and pharmacodynamics of anacetrapib, a potent cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects
Rising single doses of anacetrapib were tested in fasted and fed healthy subjects to characterize its safety, tolerability, pharmacokinetics, and pharmacodynamics, and to preliminarily assess the effects of food, age, sex, and obesity. Anacetrapib was rapidly absorbed, with peak concentrations around 4 hours post-dose and an apparent terminal half-life of about 9 to 62 hours fasted versus 42 to 83 hours fed; plasma AUC and Cmax rose less than dose-proportionally in the fasted state with an apparent absorption plateau at higher doses. Single doses markedly and dose-dependently inhibited serum CETP activity, with peak inhibition of about 90% at Tmax and about 58% at 24 hours, described by an Emax model with an EC50 of about 22 nM. A low-fat meal raised anacetrapib exposure two- to three-fold and a high-fat meal by six- to eight-fold, while pharmacokinetics and pharmacodynamics were similar across elderly versus young, women versus men, and obese versus non-obese adults, and anacetrapib was well tolerated with no meaningful blood pressure increase.
Original abstract
Aims: Anacetrapib is an orally active and potent inhibitor of CETP in development for the treatment of dyslipidaemia. These studies endeavoured to establish the safety, tolerability, pharmacokinetics and pharmacodynamics of rising single doses of anacetrapib, administered in fasted or fed conditions, and to preliminarily assess the effect of food, age, gender and obesity on the single-dose pharmacokinetics and pharmacodynamics of anacetrapib.
Methods: Safety, tolerability, anacetrapib concentrations and CETP activity were evaluated.
Results: Anacetrapib was rapidly absorbed, with peak concentrations occurring at approximately 4 h post-dose and an apparent terminal half-life ranging from approximately 9 to 62 h in the fasted state and from approximately 42 to approximately 83 h in the fed state. Plasma AUC and C(max) appeared to increase in a less than approximately dose-dependent manner in the fasted state, with an apparent plateau in absorption at higher doses. Single doses of anacetrapib markedly and dose-dependently inhibited serum CETP activity with peak effects of approximately 90% inhibition at t(max) and approximately 58% inhibition at 24 h post-dose. An E(max) model best described the plasma anacetrapib concentration vs CETP activity relationship with an EC(50) of approximately 22 nm. Food increased exposure to anacetrapib; up to approximately two-three-fold with a low-fat meal and by up to approximately six-eight fold with a high-fat meal. Anacetrapib pharmacokinetics and pharmacodynamics were similar in elderly vs young adults, women vs men, and obese vs non-obese young adults. Anacetrapib was well tolerated and was not associated with any meaningful increase in blood pressure.
Conclusions: Whereas food increased exposure to anacetrapib significantly, age, gender and obese status did not meaningfully influence anacetrapib pharmacokinetics and pharmacodynamics.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.